Urogenital schistosomiasis (UGS) is a parasitic infection that afflicts >110 million people, 3 million of whom live in Ghana. Prevalence remains high despite mass drug administration (MDA). MDA does not address the issues of environmental exposure to the parasite or risky behaviors that occur in the absence of water and sanitation infrastructure; thus, MDA is unable to reduce prevalence below 5-15%. There is a critical need for strategies that disrupt the multi-host schistosome lifecycle and thereby prevent reinfection. Our goal is to develop a public health engineering intervention package that reduces the incidence of Schistosoma haematobium infection in rural sub-Saharan Africa by combining water infrastructure, education and chemotherapy to interrupt parasite excretion, water contamination, and infection acquisition. We will determine the effect of installing wells and water recreation areas, combined with education and chemotherapy, on the rate of schistosome infection in 8 rural Ghanaian towns as compared with 4 control towns that will not receive any infrastructure. Our central hypothesis is that this combination of interventions will significantly reduce schistosome infection compared to chemotherapy alone. The rationale for the clinical trial is that, once efficacy is demonstrated, our program can be expanded to the regional and national scale. Given our strong preliminary data regarding the benefits of engineered infrastructure, our hypothesis will be tested by pursuing four specific aims: (1) measure the cross-sectional prevalence of S. haematobium infection in year 0 (baseline); (2) measure the incidence of infection with S. haematobium in the presence of various control measures (infrastructure, chemotherapy, education); (3) Assess the cost-effectiveness of each individual control measure; and (4) conduct annual knowledge, attitudes, and practices (KAP) surveys to identify specific factors that influence behavior change in the presence and absence of interventions. We expect S. haematobium incidence to be < 1% per year through a package of interventions that address the issue of repeated schistosome exposure. Our project is innovative, as it will lead to the sustainable primary prevention of infection at the community scale in rural West Africa. Our research is significant because it will quantify and document benefits that accrue as a result of a comprehensive, integrated approach to UGS prevention, which should increase communal and national willingness to adopt and sustain this package of interventions.